Structural Biology

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Jim Smith group

The molecular basis of mesoderm formation

The different cell types of the body are formed in the right place and at the right time in response to signals that are produced by special organiser regions of the embryo. These so-called morphogens act in a concentration-dependent manner to induce the formation of different cell types at different positions within developing tissues. One of the earliest interactions of this kind is mesoderm induction, which results in the formation of organs and cell types such as heart, muscle, kidney and bone.

We use frog, zebrafish and mouse embryos to study mesoderm-inducing factors and to ask how cells respond to them. In particular we use imaging approaches to understand how the signals exert long-range effects in the embryo, as well as biochemical and mathematical approaches to ask how cells distinguish between different morphogen concentrations to activate different developmental pathways. We also use a range of molecular techniques to identify the genes that are activated by these signalling pathways and which go on to activate the genetic regulatory networks that result in the formation of specific cell types. We hope that our work will help in efforts to direct stem cells down the desired developmental pathways.

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Use of bimolecular fluorescence complementation reveals that signalling by nodal family members is strong near the margin of the zebrafish embryo (bottom of image) and weak near the animal pole (top).